Human cytomegalovirus infection of Caco-2 cells occurs at the basolateral membrane and is differentiation state dependent

Epithelial cells are known to be a major target for human cytomegalovirus ( HCMV) infection; however, the analysis of virus-cell interactions has been difficult to approach due to the lack of in vitro models. In this study, we established a polarized epithelial cell model using a colon epithelial cel l derived cell line (Caco-2) that is susceptible to HCMV infection at early stages of cellular differentiation. infection of polarized cells was restr icted to the basolateral surface whereas virus was released apically, which was consistent with the apical and not basolateral surface localization of two essential viral glycoproteins, gB and gH. HCMV infection resulted in t he development of a cytopathology characteristic of HCMV infection of colon epithelium in vivo, and infection did not spread from fell to cell. The in ability of HCMV to infect Caco-2 cells at late stages of differentiation wa s due to a restriction at the level of viral entry and was consistent with the sequestration of a cellular receptor for HCMV. These observations provi de the first evidence that restriction of HCMV replication in epithelial ce lls is due to a receptor-mediated phenomenon.